rs373597415

Variant names:

• chr20-35246882-C-A
• rs373597415
• NM_006690.4:c.289C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-35246882-C-A
• chr20-35246882-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_006690.4(MMP24):​c.289C>A​(p.Arg97Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP24 NM_006690.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 2 publications found

Genes affected

MMP24 (HGNC:7172): (matrix metallopeptidase 24) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]

MMP24-AS1-EDEM2 (HGNC:):

MMP24OS (HGNC:44421): (MMP24 opposite strand)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BP7: Synonymous conserved (PhyloP=2.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP24	NM_006690.4	MANE Select	c.289C>A	p.Arg97Arg	synonymous	Exon 2 of 9	NP_006681.1	Q9Y5R2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-462-10691G>T		intron	N/A	NP_001341937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP24	ENST00000246186.8	TSL:1 MANE Select	c.289C>A	p.Arg97Arg	synonymous	Exon 2 of 9	ENSP00000246186.6	Q9Y5R2
	MMP24	ENST00000927316.1		c.289C>A	p.Arg97Arg	synonymous	Exon 2 of 8	ENSP00000597375.1
	MMP24	ENST00000927315.1		c.289C>A	p.Arg97Arg	synonymous	Exon 2 of 8	ENSP00000597374.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373597415; hg19: chr20-33834685;